Crosstalk of ischemic cardiomyocytes to the coronary microcirculation: roles of ANP and BNP

• Applicant: Professorin Dr. Michaela Kuhn
• Subject Area: Anatomy and Physiology ; Cardiology, Angiology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 456297023

Microvascular dysfunction after acute myocardial infarction (MI) is a major clinical problem. Although primary percutaneous coronary intervention (PCI) has markedly improved patients survival, despite epicardial reperfusion more than 30% of patients show signs of microvascular dysfunction leading to adverse left ventricular remodeling and heart failure. Acutely, vasoconstriction and thrombotic occlusion can reduce microvascular perfusion within the distal myocardium (“no-reflow”). Later, impaired angiogenesis can contribute to myocardial tissue damage. Based on experimental studies, several clinical trials aimed to improve myocardial angiogenesis via intracoronary administration of vascular growth factors, gene transfer or bone marrow mononuclear cells, in patients who had successful primary PCI, but the results were disappointing. A better knowledge of the cellular pathways regulating myocardial (re)perfusion after ischemia is necessary to search for therapeutic strategies capable to restore the microvascular network and flow. The here proposed project aims to elucidate the role of atrial (ANP) and B-type natriuretic peptides (BNP) in the paracrine communication of cardiomyocytes with coronary microcirculatory endothelial cells and pericytes, as well as the potential pharmacological, therapeutical implications. Based on our previous observations in the retinal and skeletal muscle microcirculation we hypothesize that: i) these cardiomyocyte hormones can prevent acute pericyte-mediated microcirculatory constrictions and stimulate pericyte-endothelial interactions and thereby angiogenesis induction; ii) chronic ischemia and inflammation may impair the microcirculatory actions of ANP and BNP through altered receptor signaling and enhanced peptide clearance; and iii) pharmacological or genetic rescue of such alterations improves myocardial reperfusion after MI.

• DFG Programme: Research Grants